Oren Cohen

Getting ready to move: transmitted information in the corticospinal pathway during preparation for movement.

Corticospinal interactions are considered to play a key role in executing voluntary movements. Nonetheless several different studies have shown directly and indirectly that these interactions take place long before movement starts, when preparation for forthcoming movements dominates. When motor-related parameters are continuously processed in several premotor cortical sites, segmental circuitry is directly exposed to this processing via descending pathways which originate from these sites in parallel to descending fibers that derive from primary motor cortex. Recent studies have highlighted the functional role of these interactions in priming downstream elements for the ensuing motor actions. Time-resolved analysis has further emphasized the dynamic properties of pre-movement preparatory activity.

Serum Cu/Zn superoxide dismutase activity is reduced in sporadic amyotrophic lateral sclerosis patients

Accumulated evidence implies that mutations in the gene coding for Cu/Zn superoxide dismutase (SOD) are associated with the pathogenesis of the familial form of amyotrophic lateral sclerosis (ALS). The clinical and pathological similarities of the familial and the sporadic forms of the disease may suggest that abnormal SOD activity takes also part in the pathogenesis of sporadic ALS. We therefore measured serum SOD activity in fifteen sporadic ALS patients. Mean serum SOD activity was 1.15 +/- 0.40 u/ml in ALS patients, 1.50 +/- 0.45 u/ml. in patients with other neurological disorders and 1.45 +/- 0.45 u/ml in.healthy controls (p < 0.021 and p < 0.031 respectively). If this sporadic ALS-related reduction in serum SOD activity will be confirmed in the diseased nervous system tissue, it may suggest that abnormal SOD activity is also associated with the motor neuron damage in the sporadic form of ALS.

Computation in spinal circuitry: lessons from behaving primates.

Performing voluntary motor actions requires the translation of motor commands into a specific set of muscle activation. While it is assumed that this process is carried out via cooperative interactions between supraspinal and spinal neurons, the unique contribution of each of these areas to the process is still unknown. Many studies have focused on the neuronal representation of the motor command, mostly in the motor cortex. Nonetheless, to execute these commands there must be a mechanism that can translate this representation into a sustained drive to the spinal motoneurons (MNs). Here we review different candidate mechanisms for activating MNs and their possible role in voluntary movements. We discuss recent studies which directly estimate the contribution of segmental INs to the transmission of cortical command to MNs, both in terms of functional connectivity and as a computational link. Finally, we suggest a conceptual framework in which the cortical motor command is processed simultaneously via MNs and INs. In this model, the motor cortex provides a transient signal which is important for initiating new patterns of recruited muscles, whereas the INs translate this command into a sustained, amplified and muscle-based signal which is necessary to maintain ongoing muscle activity.

Intrafamilial heterogeneity of movement disorders : Report of three cases in one family

Abstract We report three members of a single family with an apparently autosomal dominant, nonparoxysmal, hyperkinetic movement disorder with onset in adolescence. The proband, a 56-year-old woman, manifested dystonia, tremor and myoclonus; one of her daughters exhibited myoclonus with tremor, and the other demonstrated myoclonus with chorea later accompanied by tremor and dystonia. The slowly progressive but not debilitating symptoms were restricted to the head, arms and hands and were only moderately affected by alcohol. Laboratory investigations failed to identify any abnormality, and linkage analysis excluded the region containing the DYT1 locus, indicating that the gene responsible for idiopathic torsion dystonia was not implicated in this family. While this disorder shares manifestations with myoclonic dystonia, essential myoclonus and benign chorea, the marked intrafamilial heterogeneity and the sex-limited phenotype expressed only in females of two generations appear to be unique.

Seizures induced by frustration and despair due to unresolved moral and political issues: a rare case of reflex epilepsy.

We present a case of reflex-induced simple partial seizures, triggered by feelings of frustration, anger and despair. Such emotions were provoked by pondering over complex national and international, political and moral issues. The present case may suggest that activation of right temporal networks may mediate negative and adverse emotions induced by preoccupation with agitating, controversial issues.

An assumption-free quantification of neural responses to electrical stimulations

BACKGROUND Connectivity between brain regions provides the fundamental infrastructure for information processing. The standard way to characterize these interactions is to stimulate one site while recording the evoked response from a second site. The average stimulus-triggered response is usually compared to the pre-stimulus activity. This requires a set of prior assumptions regarding the amplitude and duration of the evoked response. NEW METHOD We introduce an assumption-free method for detecting and clustering evoked responses. We used Independent Component Analysis to reduce the dimensions of the response vectors, and then clustered them according to a Gaussian mixture model. This enables both the detection and categorization of responsive sites into different subtypes. RESULTS Our method is demonstrated on recordings obtained from the sensory-motor cortex of behaving primates in response to stimulation of the cerebello-thalamo-cortical tract. We detected and classified the evoked responses of local field potential (LFP) and local spiking activity (multiunit activity-MUA). We found a strong association between specific input (LFP) and output (MUA) patterns across cortical sites, further supporting the physiological relevance of the proposed method. COMPARISON WITH EXISTING METHODS Our method detected the vast majority of sites found in the conventional, significant threshold-crossing method. However, we found a subgroup of sites with a robust response that were missed when using the conventional method. CONCLUSION Our method provides a useful, assumption-free tool for detecting and classifying neural evoked responses in a physiologically-relevant manner.

Mssbauer study of magnetic order in RBa2Fe3O8

Complete replacement of copper by iron in RBa2Cu3O7 leads to RBa2Fe3O8 (R=Y, rare earth). Mössbauer spectroscopy measurements of57Fe and151Eu in RBa2Fe3O8 (R=Y, Eu, Ho, Er) at temperatures 4.2–800 K have been performed. Some of the spectra reveal two inequivalent iron sites, probably corresponding to iron in the Fe(2) site (fivefold oxygen coordination) and in the Fe(1) site (octahedral oxygen coordination). In all compounds the iron moments order antiferromagnetically at the same Néel temperatureTN≈720 K. The151Eu Mössbauer spectra of EuBa2Fe3O8 show that the Eu ion is trivalent and exposed to a small exchange field from the iron sublattices.

Spatiotemporal organization of neuronal activity in the cervical cord of behaving primates.

Spinal neurons operate as a processing link that integrates descending and peripheral information and in turn, generates a specific yet complex muscle command. The functional organization of spinal circuitry during normal motor behavior dictates the way in which this translation process is achieved. Nonetheless, little is known about this organization during normal motor behavior. We examined the spatial organization of neural activity in the cervical spinal cord of behaving primates performing an isometric wrist task by estimating the averaged intraspinal activity of neuronal populations. We measured population response profiles and frequency content around torque onset and tested the tendency of these profiles to exhibit a specific organization within the spinal volume. We found that the spatial distribution of characteristic response profiles was non-uniform; namely, sites with a specific response profile tended to have a preferred spatial localization. Physiologically, this finding suggests that specific spinal circuitry that controls a unique feature of motor actions (with a particular task-related response pattern) may have a segregated spinal organization. Second, attempts to restore motor function via intraspinal stimulation may be more successful when the spatial distribution of these task-related profiles is taken into account.

Reversible block of cerebellar outflow reveals cortical circuitry for motor coordination

Coordinated movements are achieved by selecting muscles and activating them at specific times. This process relies on intact cerebellar circuitry, as demonstrated by motor impairments triggered by cerebellar lesions. Based on anatomical connectivity and symptoms observed in cerebellar patients, we hypothesized that cerebellar dysfunction should disrupt the temporal patterns of motor cortical activity but not the selected motor plan. To test this hypothesis, we reversibly blocked cerebellar outflow in primates while monitoring motor behavior and neural activity. This manipulation replicated the impaired motor timing and coordination characteristic of cerebellar ataxia. We found extensive changes in motor cortical activity, including a loss of response transients at movement onset and a decoupling of task-related activity. Nonetheless, the spatial tuning of cells was unaffected and their early preparatory activity was mostly intact. These results indicate that the timing of actions, but not the selection of muscles, is regulated through cerebellar control of motor cortical activity. HIGHLIGHTS High frequency stimulation blocked cerebellar outflow and impaired motor behavior Response patterns and coordinated firing of CTC neurons were disrupted The spatial tuning and early preparatory activity of neurons were unaffected Cerebellar control of local and global cortical synchrony supports motor timing IN BRIEF Nashef et al. used high frequency stimulation to block cerebellar outflow. This manipulation impaired motor timing and coordination similarly to symptoms found in cerebellar patients. In parallel, the response patterns of cortical neurons and cell-to-cell synchronization were altered, yet spatial tuning was maintained. Motor timing and coordination are regulated by a dedicated cerebellar signal that organizes execution-related activity of a motor cortical subnetwork.

Cerebellar Shaping of Motor Cortical Firing Is Correlated with Timing of Motor Actions

In higher mammals, motor timing is considered to be dictated by cerebellar control of motor cortical activity, relayed through the cerebellar-thalamo-cortical (CTC) system. Nonetheless, the way cerebellar information is integrated with motor cortical commands and affects their temporal properties remains unclear. To address this issue, we activated the CTC system in primates and found that it efficiently recruits motor cortical cells; however, the cortical response was dominated by prolonged inhibition that imposed a directional activation across the motor cortex. During task performance, cortical cells that integrated CTC information fired synchronous bursts at movement onset. These cells expressed a stronger correlation with reaction time than non-CTC cells. Thus, the excitation-inhibition interplay triggered by the CTC system facilitates transient recruitment of a cortical subnetwork at movement onset. The CTC system may shape neural firing to produce the required profile to initiate movements and thus plays a pivotal role in timing motor actions.